Epilepsy & Seizures

NEW ORLEANS – Risk for sudden unexpected death in epilepsy (SUDEP) may change over time and yearly patient risk assessments are advisable, based on study results presented at the annual meeting of the American Epilepsy Society.

Based on 3 years of data collected from over 12,000 people with epilepsy, 27.0% who had been at high risk (three or more generalized tonic-clonic seizures [GTCs] per year) at baseline moved out of the high-risk category. In addition, 32.5% at medium risk (one to two GTCs per year) at baseline changed categories. Finally, 7.0% in the low-risk category (no GTC seizures in the last year) at baseline moved to a higher-risk category.

“An individual’s risk [of SUDEP] is not set in stone,” said Neishay Ayub, MD, of Beth Israel Deaconess Medical Center, Boston, who presented the data at the meeting. “Our findings support the recommendation that for people with epilepsy who have ongoing generalized tonic-clonic seizures, the goal of treatment is to reduce GTCs and thereby lower SUDEP risk.”

A 2017 practice guideline summary from the American Academy of Neurology and the American Epilepsy Society identified the presence and frequency of GTCs and absence of seizure freedom as risk factors for SUDEP. Using these measures, Dr. Ayub and colleagues sought to stratify patients according to their risk of SUDEP and monitor how risk changed over time. They collected information about more than 1.4 million seizures that occurred from December 2007 to February 2018 in 12,402 users of the electronic diary Seizure Tracker.

For each user, the researchers calculated the number of generalized seizures for each year since the initial seizure diary entry. They categorized each user as being at low, medium, or high risk of SUDEP during each year. Low risk was defined as no generalized seizures in a year. Medium risk was defined as one or two generalized seizures in a year. High risk was defined as three or more generalized seizures in a year.

“The next step would be to see if we can confirm this patient-reported data with an objective study to determine when seizures did or did not occur,” said Daniel Goldenholz, MD, PhD, also of Beth Israel Deaconess Medical Center and senior author of the study. “For example, assessing information using new FDA [Food and Drug Administration]-approved wearable seizure tracker devices could give us a more comprehensive picture.”

The study was funded by the Harvard School of Public Health, Boston.

[email protected]

SOURCE: Ayub N et al. AES 2018, Abstract 2.158.

NEW ORLEANS – Risk for sudden unexpected death in epilepsy (SUDEP) may change over time and yearly patient risk assessments are advisable, based on study results presented at the annual meeting of the American Epilepsy Society.

Based on 3 years of data collected from over 12,000 people with epilepsy, 27.0% who had been at high risk (three or more generalized tonic-clonic seizures [GTCs] per year) at baseline moved out of the high-risk category. In addition, 32.5% at medium risk (one to two GTCs per year) at baseline changed categories. Finally, 7.0% in the low-risk category (no GTC seizures in the last year) at baseline moved to a higher-risk category.

“An individual’s risk [of SUDEP] is not set in stone,” said Neishay Ayub, MD, of Beth Israel Deaconess Medical Center, Boston, who presented the data at the meeting. “Our findings support the recommendation that for people with epilepsy who have ongoing generalized tonic-clonic seizures, the goal of treatment is to reduce GTCs and thereby lower SUDEP risk.”

A 2017 practice guideline summary from the American Academy of Neurology and the American Epilepsy Society identified the presence and frequency of GTCs and absence of seizure freedom as risk factors for SUDEP. Using these measures, Dr. Ayub and colleagues sought to stratify patients according to their risk of SUDEP and monitor how risk changed over time. They collected information about more than 1.4 million seizures that occurred from December 2007 to February 2018 in 12,402 users of the electronic diary Seizure Tracker.

For each user, the researchers calculated the number of generalized seizures for each year since the initial seizure diary entry. They categorized each user as being at low, medium, or high risk of SUDEP during each year. Low risk was defined as no generalized seizures in a year. Medium risk was defined as one or two generalized seizures in a year. High risk was defined as three or more generalized seizures in a year.

“The next step would be to see if we can confirm this patient-reported data with an objective study to determine when seizures did or did not occur,” said Daniel Goldenholz, MD, PhD, also of Beth Israel Deaconess Medical Center and senior author of the study. “For example, assessing information using new FDA [Food and Drug Administration]-approved wearable seizure tracker devices could give us a more comprehensive picture.”

The study was funded by the Harvard School of Public Health, Boston.

[email protected]

SOURCE: Ayub N et al. AES 2018, Abstract 2.158.

NEW ORLEANS – Risk for sudden unexpected death in epilepsy (SUDEP) may change over time and yearly patient risk assessments are advisable, based on study results presented at the annual meeting of the American Epilepsy Society.

Based on 3 years of data collected from over 12,000 people with epilepsy, 27.0% who had been at high risk (three or more generalized tonic-clonic seizures [GTCs] per year) at baseline moved out of the high-risk category. In addition, 32.5% at medium risk (one to two GTCs per year) at baseline changed categories. Finally, 7.0% in the low-risk category (no GTC seizures in the last year) at baseline moved to a higher-risk category.

“An individual’s risk [of SUDEP] is not set in stone,” said Neishay Ayub, MD, of Beth Israel Deaconess Medical Center, Boston, who presented the data at the meeting. “Our findings support the recommendation that for people with epilepsy who have ongoing generalized tonic-clonic seizures, the goal of treatment is to reduce GTCs and thereby lower SUDEP risk.”

A 2017 practice guideline summary from the American Academy of Neurology and the American Epilepsy Society identified the presence and frequency of GTCs and absence of seizure freedom as risk factors for SUDEP. Using these measures, Dr. Ayub and colleagues sought to stratify patients according to their risk of SUDEP and monitor how risk changed over time. They collected information about more than 1.4 million seizures that occurred from December 2007 to February 2018 in 12,402 users of the electronic diary Seizure Tracker.

For each user, the researchers calculated the number of generalized seizures for each year since the initial seizure diary entry. They categorized each user as being at low, medium, or high risk of SUDEP during each year. Low risk was defined as no generalized seizures in a year. Medium risk was defined as one or two generalized seizures in a year. High risk was defined as three or more generalized seizures in a year.

“The next step would be to see if we can confirm this patient-reported data with an objective study to determine when seizures did or did not occur,” said Daniel Goldenholz, MD, PhD, also of Beth Israel Deaconess Medical Center and senior author of the study. “For example, assessing information using new FDA [Food and Drug Administration]-approved wearable seizure tracker devices could give us a more comprehensive picture.”

The study was funded by the Harvard School of Public Health, Boston.

[email protected]

SOURCE: Ayub N et al. AES 2018, Abstract 2.158.

NEW ORLEANS – Depression severity is correlated with seizure frequency and quality of life in adults with epilepsy, according to an analysis presented at the annual meeting of the American Epilepsy Society.

The conclusion comes from a study of 120 people with epilepsy, 62 of whom had at least moderate depression based on the Patient Health Questionnaire-9 (PHQ-9). The Rapid Estimate of Adult Literacy in Medicine (REALM-R), Quality of Life in Epilepsy (QOLIE-10) and Charlson Comorbidity Index were used to assess patients’ health literacy, quality of life, and medical comorbidity, respectively

Among demographic characteristics, only inability to work was significantly associated with depression severity. Higher 30-day seizure frequency, panic disorder, and obsessive-compulsive disorder were correlated with more severe depression severity. Medical comorbidity was not associated with increased risk of depression.

Identifying and treating psychiatric comorbidities should be part of the management of patients with epilepsy, said Martha X. Sajatovic, MD, director of the Neurological and Behavioral Outcomes Center at Case Western Reserve University in Cleveland, who presented the data. “Following up to ensure they receive treatment is vital, because it can truly change patient outcomes and help them achieve their best quality of life.”

The study findings are consistent with those of previous research indicating that people with symptoms of depression are more likely to have more frequent seizures and decreased quality of life, said Dr. Sajatovic.

“Health care providers should screen their epilepsy patients for depression, but they shouldn’t stop there,” she advised. “A person may have depressive symptoms that don’t reach the level of depression but should be assessed for other types of mental health issues that could easily be overlooked.”

Patients with epilepsy should respond to the PHQ-9 annually, or more frequently, if warranted, she added.

“It’s important that people with epilepsy who have depression or other mental health issues get treatment such as cognitive behavioral therapy and medication,” said Dr. Sajatovic. “Even being in a self-management program helps, because the better they are at self management, the less likely they are to suffer negative health effects.”

This study was supported by a grant from the Centers for Disease Control and Prevention SIP 14-007 1U48DP005030.
 

[email protected]

SOURCE: Kumar N et al. AES 2018, Abstract 1.371.

NEW ORLEANS – Depression severity is correlated with seizure frequency and quality of life in adults with epilepsy, according to an analysis presented at the annual meeting of the American Epilepsy Society.

The conclusion comes from a study of 120 people with epilepsy, 62 of whom had at least moderate depression based on the Patient Health Questionnaire-9 (PHQ-9). The Rapid Estimate of Adult Literacy in Medicine (REALM-R), Quality of Life in Epilepsy (QOLIE-10) and Charlson Comorbidity Index were used to assess patients’ health literacy, quality of life, and medical comorbidity, respectively

Among demographic characteristics, only inability to work was significantly associated with depression severity. Higher 30-day seizure frequency, panic disorder, and obsessive-compulsive disorder were correlated with more severe depression severity. Medical comorbidity was not associated with increased risk of depression.

Identifying and treating psychiatric comorbidities should be part of the management of patients with epilepsy, said Martha X. Sajatovic, MD, director of the Neurological and Behavioral Outcomes Center at Case Western Reserve University in Cleveland, who presented the data. “Following up to ensure they receive treatment is vital, because it can truly change patient outcomes and help them achieve their best quality of life.”

The study findings are consistent with those of previous research indicating that people with symptoms of depression are more likely to have more frequent seizures and decreased quality of life, said Dr. Sajatovic.

“Health care providers should screen their epilepsy patients for depression, but they shouldn’t stop there,” she advised. “A person may have depressive symptoms that don’t reach the level of depression but should be assessed for other types of mental health issues that could easily be overlooked.”

Patients with epilepsy should respond to the PHQ-9 annually, or more frequently, if warranted, she added.

“It’s important that people with epilepsy who have depression or other mental health issues get treatment such as cognitive behavioral therapy and medication,” said Dr. Sajatovic. “Even being in a self-management program helps, because the better they are at self management, the less likely they are to suffer negative health effects.”

This study was supported by a grant from the Centers for Disease Control and Prevention SIP 14-007 1U48DP005030.
 

[email protected]

SOURCE: Kumar N et al. AES 2018, Abstract 1.371.

NEW ORLEANS – Depression severity is correlated with seizure frequency and quality of life in adults with epilepsy, according to an analysis presented at the annual meeting of the American Epilepsy Society.

The conclusion comes from a study of 120 people with epilepsy, 62 of whom had at least moderate depression based on the Patient Health Questionnaire-9 (PHQ-9). The Rapid Estimate of Adult Literacy in Medicine (REALM-R), Quality of Life in Epilepsy (QOLIE-10) and Charlson Comorbidity Index were used to assess patients’ health literacy, quality of life, and medical comorbidity, respectively

Among demographic characteristics, only inability to work was significantly associated with depression severity. Higher 30-day seizure frequency, panic disorder, and obsessive-compulsive disorder were correlated with more severe depression severity. Medical comorbidity was not associated with increased risk of depression.

Identifying and treating psychiatric comorbidities should be part of the management of patients with epilepsy, said Martha X. Sajatovic, MD, director of the Neurological and Behavioral Outcomes Center at Case Western Reserve University in Cleveland, who presented the data. “Following up to ensure they receive treatment is vital, because it can truly change patient outcomes and help them achieve their best quality of life.”

The study findings are consistent with those of previous research indicating that people with symptoms of depression are more likely to have more frequent seizures and decreased quality of life, said Dr. Sajatovic.

“Health care providers should screen their epilepsy patients for depression, but they shouldn’t stop there,” she advised. “A person may have depressive symptoms that don’t reach the level of depression but should be assessed for other types of mental health issues that could easily be overlooked.”

Patients with epilepsy should respond to the PHQ-9 annually, or more frequently, if warranted, she added.

“It’s important that people with epilepsy who have depression or other mental health issues get treatment such as cognitive behavioral therapy and medication,” said Dr. Sajatovic. “Even being in a self-management program helps, because the better they are at self management, the less likely they are to suffer negative health effects.”

This study was supported by a grant from the Centers for Disease Control and Prevention SIP 14-007 1U48DP005030.
 

[email protected]

SOURCE: Kumar N et al. AES 2018, Abstract 1.371.

NEW ORLEANS – Patients taking enzyme-inducing antiepileptic drugs (AEDs) may require a clinically meaningful increase in their vitamin D doses to achieve the same 25-hydroxyvitamin D (25[OH]D) plasma levels as patients taking nonenzyme-inducing AEDs, based on a retrospective chart review presented at the annual meeting of the American Epilepsy Society.

While patients receiving either type of AED had similar average 25(OH)D levels in the study (32.0 ng/mL in the enzyme-inducing AED group and 33.2 ng/mL in the noninducing AED group), those in the enzyme-inducing group required 1,587 U/day to meet the goal – a 409-unit increase in dose, compared with the 1,108 U/day dose taken by patients in the nonenzyme-inducing group.

“Patients taking enzyme-inducing AEDs may benefit from more intensive monitoring of their vitamin D supplementation, and clinicians should anticipate this likely pharmacokinetic interaction,” said Barry E. Gidal, PharmD, professor of pharmacy and neurology at the University of Wisconsin–Madison, and his colleagues.

Researchers have suggested that enzyme-inducing AEDs may affect CYP450 isoenzymes, increase vitamin D metabolism, and reduce 25(OH)D plasma levels. “It follows … that a potential pharmacokinetic interaction could exist between enzyme-inducing AEDs and oral formulations of vitamin D used for supplementation,” the investigators said.

To test the hypothesis, Dr. Gidal and his colleagues reviewed the charts of patients with epilepsy who were on any AED regimen and were prescribed vitamin D at William S. Middleton Memorial Veterans Hospital in Madison, Wisconsin, between January 2013 and September 2017.

The researchers grouped patients by those using enzyme-inducing AEDs and those taking noninducing AEDs. Patients who were taking AEDs in both categories were placed in the enzyme-inducing AED group. Patients with malabsorptive conditions and patients using calcitriol were excluded from the analysis.

Data included AEDs used, prescription and over-the-counter vitamin D use, 25(OH)D plasma concentration, renal function, age, gender, and ethnicity. Patients’ 25(OH)D levels were measured using a chemiluminescence immunoassay, and a minimum 25(OH)D plasma level of 30 ng/mL was the therapeutic goal.

The multivariant analysis was adjusted for potentially confounding variables including 25(OH)D concentration, over-the-counter vitamin D use, chronic kidney disease, age, gender, and ethnicity.

The analysis included 1,113 observations from 315 patients, and 263 of the observations (23.6%) were in the enzyme-inducing AED group. The enzyme-inducing group and noninducing groups were mostly male (90.5% and 91.8%, respectively) and similar in average age (65.9 and 61.4 years, respectively). Variables were evenly distributed between the groups, with the exceptions of chronic kidney disease, which was less common in the enzyme-inducing group (6.1% vs. 13.8%), and ethnicity (78.7% Caucasian in the enzyme-inducing group vs. 87.7% Caucasian in the noninducing group). The most common enzyme-inducing AED was phenytoin (50.6%), followed by carbamazepine (31.9%), phenobarbital (14.1%), oxcarbazepine (6.8%), primidone (1.9%), and eslicarbazepine (0.8%).

Dr. Gidal reported honoraria from Eisai, Sunovion, Lundbeck, and GW Pharmaceuticals.
 

[email protected]

SOURCE: Gidal BE et al. AES 2018, Abstract 1.315.

NEW ORLEANS – Patients taking enzyme-inducing antiepileptic drugs (AEDs) may require a clinically meaningful increase in their vitamin D doses to achieve the same 25-hydroxyvitamin D (25[OH]D) plasma levels as patients taking nonenzyme-inducing AEDs, based on a retrospective chart review presented at the annual meeting of the American Epilepsy Society.

While patients receiving either type of AED had similar average 25(OH)D levels in the study (32.0 ng/mL in the enzyme-inducing AED group and 33.2 ng/mL in the noninducing AED group), those in the enzyme-inducing group required 1,587 U/day to meet the goal – a 409-unit increase in dose, compared with the 1,108 U/day dose taken by patients in the nonenzyme-inducing group.

“Patients taking enzyme-inducing AEDs may benefit from more intensive monitoring of their vitamin D supplementation, and clinicians should anticipate this likely pharmacokinetic interaction,” said Barry E. Gidal, PharmD, professor of pharmacy and neurology at the University of Wisconsin–Madison, and his colleagues.

Researchers have suggested that enzyme-inducing AEDs may affect CYP450 isoenzymes, increase vitamin D metabolism, and reduce 25(OH)D plasma levels. “It follows … that a potential pharmacokinetic interaction could exist between enzyme-inducing AEDs and oral formulations of vitamin D used for supplementation,” the investigators said.

To test the hypothesis, Dr. Gidal and his colleagues reviewed the charts of patients with epilepsy who were on any AED regimen and were prescribed vitamin D at William S. Middleton Memorial Veterans Hospital in Madison, Wisconsin, between January 2013 and September 2017.

The researchers grouped patients by those using enzyme-inducing AEDs and those taking noninducing AEDs. Patients who were taking AEDs in both categories were placed in the enzyme-inducing AED group. Patients with malabsorptive conditions and patients using calcitriol were excluded from the analysis.

Data included AEDs used, prescription and over-the-counter vitamin D use, 25(OH)D plasma concentration, renal function, age, gender, and ethnicity. Patients’ 25(OH)D levels were measured using a chemiluminescence immunoassay, and a minimum 25(OH)D plasma level of 30 ng/mL was the therapeutic goal.

The multivariant analysis was adjusted for potentially confounding variables including 25(OH)D concentration, over-the-counter vitamin D use, chronic kidney disease, age, gender, and ethnicity.

The analysis included 1,113 observations from 315 patients, and 263 of the observations (23.6%) were in the enzyme-inducing AED group. The enzyme-inducing group and noninducing groups were mostly male (90.5% and 91.8%, respectively) and similar in average age (65.9 and 61.4 years, respectively). Variables were evenly distributed between the groups, with the exceptions of chronic kidney disease, which was less common in the enzyme-inducing group (6.1% vs. 13.8%), and ethnicity (78.7% Caucasian in the enzyme-inducing group vs. 87.7% Caucasian in the noninducing group). The most common enzyme-inducing AED was phenytoin (50.6%), followed by carbamazepine (31.9%), phenobarbital (14.1%), oxcarbazepine (6.8%), primidone (1.9%), and eslicarbazepine (0.8%).

Dr. Gidal reported honoraria from Eisai, Sunovion, Lundbeck, and GW Pharmaceuticals.
 

[email protected]

SOURCE: Gidal BE et al. AES 2018, Abstract 1.315.

NEW ORLEANS – Patients taking enzyme-inducing antiepileptic drugs (AEDs) may require a clinically meaningful increase in their vitamin D doses to achieve the same 25-hydroxyvitamin D (25[OH]D) plasma levels as patients taking nonenzyme-inducing AEDs, based on a retrospective chart review presented at the annual meeting of the American Epilepsy Society.

While patients receiving either type of AED had similar average 25(OH)D levels in the study (32.0 ng/mL in the enzyme-inducing AED group and 33.2 ng/mL in the noninducing AED group), those in the enzyme-inducing group required 1,587 U/day to meet the goal – a 409-unit increase in dose, compared with the 1,108 U/day dose taken by patients in the nonenzyme-inducing group.

“Patients taking enzyme-inducing AEDs may benefit from more intensive monitoring of their vitamin D supplementation, and clinicians should anticipate this likely pharmacokinetic interaction,” said Barry E. Gidal, PharmD, professor of pharmacy and neurology at the University of Wisconsin–Madison, and his colleagues.

Researchers have suggested that enzyme-inducing AEDs may affect CYP450 isoenzymes, increase vitamin D metabolism, and reduce 25(OH)D plasma levels. “It follows … that a potential pharmacokinetic interaction could exist between enzyme-inducing AEDs and oral formulations of vitamin D used for supplementation,” the investigators said.

To test the hypothesis, Dr. Gidal and his colleagues reviewed the charts of patients with epilepsy who were on any AED regimen and were prescribed vitamin D at William S. Middleton Memorial Veterans Hospital in Madison, Wisconsin, between January 2013 and September 2017.

The researchers grouped patients by those using enzyme-inducing AEDs and those taking noninducing AEDs. Patients who were taking AEDs in both categories were placed in the enzyme-inducing AED group. Patients with malabsorptive conditions and patients using calcitriol were excluded from the analysis.

Data included AEDs used, prescription and over-the-counter vitamin D use, 25(OH)D plasma concentration, renal function, age, gender, and ethnicity. Patients’ 25(OH)D levels were measured using a chemiluminescence immunoassay, and a minimum 25(OH)D plasma level of 30 ng/mL was the therapeutic goal.

The multivariant analysis was adjusted for potentially confounding variables including 25(OH)D concentration, over-the-counter vitamin D use, chronic kidney disease, age, gender, and ethnicity.

The analysis included 1,113 observations from 315 patients, and 263 of the observations (23.6%) were in the enzyme-inducing AED group. The enzyme-inducing group and noninducing groups were mostly male (90.5% and 91.8%, respectively) and similar in average age (65.9 and 61.4 years, respectively). Variables were evenly distributed between the groups, with the exceptions of chronic kidney disease, which was less common in the enzyme-inducing group (6.1% vs. 13.8%), and ethnicity (78.7% Caucasian in the enzyme-inducing group vs. 87.7% Caucasian in the noninducing group). The most common enzyme-inducing AED was phenytoin (50.6%), followed by carbamazepine (31.9%), phenobarbital (14.1%), oxcarbazepine (6.8%), primidone (1.9%), and eslicarbazepine (0.8%).

Dr. Gidal reported honoraria from Eisai, Sunovion, Lundbeck, and GW Pharmaceuticals.
 

[email protected]

SOURCE: Gidal BE et al. AES 2018, Abstract 1.315.

NEW ORLEANS – Clinicians should screen patients with pediatric epilepsy for depression regularly, according to research described at the annual meeting of the American Epilepsy Society. Referral to a mental health provider is adequate for most patients with moderately severe symptoms of depression, but some patients may require active intervention during the clinical visit, said the researchers.

“We know that depression is more common in people with epilepsy, compared to the general population, but there is less information about depression in children and teens than adults, and little is known about the factors that increase the likelihood of depressive symptoms,” said Hillary Thomas, PhD, a pediatric psychologist at Children’s Medical Center in Dallas. “Depression screening should be routine at epilepsy treatment centers and can identify children and teens who would benefit from intervention.”

Following 2015 guidelines from the American Academy of Neurology, the Comprehensive Epilepsy Center at Children’s Health System in Dallas developed a behavioral health screening protocol for teens with epilepsy. The center aims to identify patients with depressive symptoms and ensure that they are referred to appropriate behavioral health practitioners. Clinicians also review the screening data and seizure variables for their potential implications for clinical care. Researchers at the center also seek to elucidate the relationship between depressive symptoms and seizure diagnosis and treatment.

As part of the protocol, Dr. Thomas and her colleagues administer the Patient Health Questionnaire-9 (adolescent version) to all patients aged 15-18 years during their visit to the epilepsy clinic. Patients with intellectual disability or other factors that prevent them from providing valid responses are excluded. If a patient’s PHQ-9 score indicates at least moderately severe depressive symptoms, or if he or she reports suicidal ideation, clinicians follow a specific response protocol that includes providing referrals, encouraging follow-up with the patient’s current mental health provider, and obtaining a suicide risk assessment from a psychologist or social worker. After the screener is completed, clinicians retrieve demographic and clinical data (e.g., seizure diagnosis, medication, number of clinic or emergency department visits) from the patient’s medical record and include them in a database for subsequent analysis.

Dr. Thomas and her colleagues presented data from 394 youth with epilepsy whom they had screened. Patients’ mean age was 16 years, and half of the population was female. The study population had rates of depression similar to those identified in previous studies, said Dr. Thomas. Approximately 87% of patients had minimal or mild depressive symptoms, and 8% had moderately severe depressive symptoms. Furthermore, 5% of the patients reported suicidal ideation or previous suicide attempt. Several of the patients with suicidal ideation had a current mental health provider, and the others required an in-clinic risk assessment. Overall, 13% of the population required behavioral health referral or intervention. When the researchers conducted chi-squared analysis, they found no significant association between seizure type and depression severity.

“Our results don’t mean that only 13% of the teens with epilepsy had depressive symptoms,” said Susan Arnold, MD, director of the Comprehensive Epilepsy Center and a coauthor of the study. “They indicate the significant percentage of teens whose level of depressive symptoms warranted behavioral health referrals or further evaluation or even intervention during a clinic visit. Health care providers need to be vigilant about continually screening children and teens for depression.” As part of each patient’s comprehensive care, epilepsy treatment centers should provide psychosocial teams that include social workers or psychologists, she added.

The investigators plan to continue analyzing the data for specific depression symptoms that are most common in teens. These symptoms could be the basis for developing additional resources for families, such as lists of warning signs and guides to symptom management, as well as group therapy and support groups.
 

[email protected]

SOURCE: Thomas HM et al. Abstract 1.388.

NEW ORLEANS – Clinicians should screen patients with pediatric epilepsy for depression regularly, according to research described at the annual meeting of the American Epilepsy Society. Referral to a mental health provider is adequate for most patients with moderately severe symptoms of depression, but some patients may require active intervention during the clinical visit, said the researchers.

“We know that depression is more common in people with epilepsy, compared to the general population, but there is less information about depression in children and teens than adults, and little is known about the factors that increase the likelihood of depressive symptoms,” said Hillary Thomas, PhD, a pediatric psychologist at Children’s Medical Center in Dallas. “Depression screening should be routine at epilepsy treatment centers and can identify children and teens who would benefit from intervention.”

Following 2015 guidelines from the American Academy of Neurology, the Comprehensive Epilepsy Center at Children’s Health System in Dallas developed a behavioral health screening protocol for teens with epilepsy. The center aims to identify patients with depressive symptoms and ensure that they are referred to appropriate behavioral health practitioners. Clinicians also review the screening data and seizure variables for their potential implications for clinical care. Researchers at the center also seek to elucidate the relationship between depressive symptoms and seizure diagnosis and treatment.

As part of the protocol, Dr. Thomas and her colleagues administer the Patient Health Questionnaire-9 (adolescent version) to all patients aged 15-18 years during their visit to the epilepsy clinic. Patients with intellectual disability or other factors that prevent them from providing valid responses are excluded. If a patient’s PHQ-9 score indicates at least moderately severe depressive symptoms, or if he or she reports suicidal ideation, clinicians follow a specific response protocol that includes providing referrals, encouraging follow-up with the patient’s current mental health provider, and obtaining a suicide risk assessment from a psychologist or social worker. After the screener is completed, clinicians retrieve demographic and clinical data (e.g., seizure diagnosis, medication, number of clinic or emergency department visits) from the patient’s medical record and include them in a database for subsequent analysis.

Dr. Thomas and her colleagues presented data from 394 youth with epilepsy whom they had screened. Patients’ mean age was 16 years, and half of the population was female. The study population had rates of depression similar to those identified in previous studies, said Dr. Thomas. Approximately 87% of patients had minimal or mild depressive symptoms, and 8% had moderately severe depressive symptoms. Furthermore, 5% of the patients reported suicidal ideation or previous suicide attempt. Several of the patients with suicidal ideation had a current mental health provider, and the others required an in-clinic risk assessment. Overall, 13% of the population required behavioral health referral or intervention. When the researchers conducted chi-squared analysis, they found no significant association between seizure type and depression severity.

“Our results don’t mean that only 13% of the teens with epilepsy had depressive symptoms,” said Susan Arnold, MD, director of the Comprehensive Epilepsy Center and a coauthor of the study. “They indicate the significant percentage of teens whose level of depressive symptoms warranted behavioral health referrals or further evaluation or even intervention during a clinic visit. Health care providers need to be vigilant about continually screening children and teens for depression.” As part of each patient’s comprehensive care, epilepsy treatment centers should provide psychosocial teams that include social workers or psychologists, she added.

The investigators plan to continue analyzing the data for specific depression symptoms that are most common in teens. These symptoms could be the basis for developing additional resources for families, such as lists of warning signs and guides to symptom management, as well as group therapy and support groups.
 

[email protected]

SOURCE: Thomas HM et al. Abstract 1.388.

NEW ORLEANS – Clinicians should screen patients with pediatric epilepsy for depression regularly, according to research described at the annual meeting of the American Epilepsy Society. Referral to a mental health provider is adequate for most patients with moderately severe symptoms of depression, but some patients may require active intervention during the clinical visit, said the researchers.

“We know that depression is more common in people with epilepsy, compared to the general population, but there is less information about depression in children and teens than adults, and little is known about the factors that increase the likelihood of depressive symptoms,” said Hillary Thomas, PhD, a pediatric psychologist at Children’s Medical Center in Dallas. “Depression screening should be routine at epilepsy treatment centers and can identify children and teens who would benefit from intervention.”

Following 2015 guidelines from the American Academy of Neurology, the Comprehensive Epilepsy Center at Children’s Health System in Dallas developed a behavioral health screening protocol for teens with epilepsy. The center aims to identify patients with depressive symptoms and ensure that they are referred to appropriate behavioral health practitioners. Clinicians also review the screening data and seizure variables for their potential implications for clinical care. Researchers at the center also seek to elucidate the relationship between depressive symptoms and seizure diagnosis and treatment.

As part of the protocol, Dr. Thomas and her colleagues administer the Patient Health Questionnaire-9 (adolescent version) to all patients aged 15-18 years during their visit to the epilepsy clinic. Patients with intellectual disability or other factors that prevent them from providing valid responses are excluded. If a patient’s PHQ-9 score indicates at least moderately severe depressive symptoms, or if he or she reports suicidal ideation, clinicians follow a specific response protocol that includes providing referrals, encouraging follow-up with the patient’s current mental health provider, and obtaining a suicide risk assessment from a psychologist or social worker. After the screener is completed, clinicians retrieve demographic and clinical data (e.g., seizure diagnosis, medication, number of clinic or emergency department visits) from the patient’s medical record and include them in a database for subsequent analysis.

Dr. Thomas and her colleagues presented data from 394 youth with epilepsy whom they had screened. Patients’ mean age was 16 years, and half of the population was female. The study population had rates of depression similar to those identified in previous studies, said Dr. Thomas. Approximately 87% of patients had minimal or mild depressive symptoms, and 8% had moderately severe depressive symptoms. Furthermore, 5% of the patients reported suicidal ideation or previous suicide attempt. Several of the patients with suicidal ideation had a current mental health provider, and the others required an in-clinic risk assessment. Overall, 13% of the population required behavioral health referral or intervention. When the researchers conducted chi-squared analysis, they found no significant association between seizure type and depression severity.

“Our results don’t mean that only 13% of the teens with epilepsy had depressive symptoms,” said Susan Arnold, MD, director of the Comprehensive Epilepsy Center and a coauthor of the study. “They indicate the significant percentage of teens whose level of depressive symptoms warranted behavioral health referrals or further evaluation or even intervention during a clinic visit. Health care providers need to be vigilant about continually screening children and teens for depression.” As part of each patient’s comprehensive care, epilepsy treatment centers should provide psychosocial teams that include social workers or psychologists, she added.

The investigators plan to continue analyzing the data for specific depression symptoms that are most common in teens. These symptoms could be the basis for developing additional resources for families, such as lists of warning signs and guides to symptom management, as well as group therapy and support groups.
 

[email protected]

SOURCE: Thomas HM et al. Abstract 1.388.

Two clinical parameters measurable at seizure onset appear to predict a return to baseline after prolonged status epilepticus (SE), based on a study of patients who presented to a single, tertiary academic medical center over a 12-year period.

Absence of nonconvulsive SE with coma and a decreasing Charlson Comorbidity Index were the only independent predictors for return to baseline in patients with SE duration greater than 48 hours, the researchers found. However, the research fell short of developing a model for identifying patients at risk for prolonged SE.

“These findings are of great clinical importance, as up to now, clinicians have had no reliable prediction tools to direct decisions regarding the level of care with progressive SE duration. Early and reliable identification of patients with potential favorable outcome despite having SE for several days is of utmost clinical importance, as this insight may urge clinicians to intensify treatment rather than consider care withdrawal as systemic and neurologic sequelae increase, and chances of SE termination decrease over time,” first author Raoul C. Sutter, MD, of University Hospital Basel (Switzerland), and his colleagues wrote about their findings in Epilepsia.

The researchers identified 467 adult patients with prolonged SE at University Hospital Basel during 2005-2016 – excluding those with SE as a consequence of hypoxic‐ischemic brain injury – who had a median age of 66.7 years and median SE duration of 1 day. While 11.8% of patients died in the hospital and 12.4% at 30 days after SE onset, 40.9% made a complete neurologic and functional recovery to their premorbid status.

There were significant differences in in-hospital outcomes between patients with different SE durations. For example, rates of returning to baseline differed significantly at 55.6% of those with a SE duration of 0-12 hours, 36.8% with 12-24 hours’ duration, 34.6% with 24-48 hours’ duration, and 25.5% with more than 48 hours.

A multivariable regression model identified absence of nonconvulsive SE with coma and a decreasing Charlson Comorbidity Index as the only independent predictors for return to baseline in patients with SE duration greater than 48 hours, and both remained significant predictors after adjustment for use of anesthetics and vasopressors. These predictors of a return to baseline after prolonged SE remained significant after excluding patients who died. This two-variable prediction model had an area under the receiver operating curve (AUROC) of 0.82, “indicating good discrimination,” and an AUROC of 0.76 following cross-validation.

The investigators also sought to develop a model to identify patients at risk for prolonged SE, but the model showed relatively poor discriminative ability with AUROCs of just 0.67-0.72 for predicting no termination of SE within 12, 24, or 48 hours. “Our attempt to generate a highly reliable prediction model for early recognition of patients at increased risk for developing prolonged SE failed, as demonstrated by the rather small AUROC and the fact that sensitivity analyses after exclusion of patients who died revealed inconsistent association of the identified predictors,” they wrote.

Prior reports identified younger age, absence of acute brain lesions at presentation, and the absence of multiple concomitant medical problems as factors associated with favorable outcome after prolonged SE, but “none of the studies performed multivariable regression models and generated or tested predictions models in this context,” they noted.

The authors cautioned that “although internal cross-validation of the final prediction model indicated adequate performance [based on an AUROC of 0.76], further external validation of our prediction model is warranted before our prediction model can be implemented and used for decision making in daily clinical practice.”

Some authors reported receiving research, travel, and/or personal grants or speaker fees from companies marketing antiepileptic drugs, such as UCB, Eisai, and GlaxoSmithKline.

[email protected]

SOURCE: Sutter RC et al. Epilepsia. 2018 Nov 22. doi: 10.1111/epi.14603

Two clinical parameters measurable at seizure onset appear to predict a return to baseline after prolonged status epilepticus (SE), based on a study of patients who presented to a single, tertiary academic medical center over a 12-year period.

Absence of nonconvulsive SE with coma and a decreasing Charlson Comorbidity Index were the only independent predictors for return to baseline in patients with SE duration greater than 48 hours, the researchers found. However, the research fell short of developing a model for identifying patients at risk for prolonged SE.

“These findings are of great clinical importance, as up to now, clinicians have had no reliable prediction tools to direct decisions regarding the level of care with progressive SE duration. Early and reliable identification of patients with potential favorable outcome despite having SE for several days is of utmost clinical importance, as this insight may urge clinicians to intensify treatment rather than consider care withdrawal as systemic and neurologic sequelae increase, and chances of SE termination decrease over time,” first author Raoul C. Sutter, MD, of University Hospital Basel (Switzerland), and his colleagues wrote about their findings in Epilepsia.

The researchers identified 467 adult patients with prolonged SE at University Hospital Basel during 2005-2016 – excluding those with SE as a consequence of hypoxic‐ischemic brain injury – who had a median age of 66.7 years and median SE duration of 1 day. While 11.8% of patients died in the hospital and 12.4% at 30 days after SE onset, 40.9% made a complete neurologic and functional recovery to their premorbid status.

There were significant differences in in-hospital outcomes between patients with different SE durations. For example, rates of returning to baseline differed significantly at 55.6% of those with a SE duration of 0-12 hours, 36.8% with 12-24 hours’ duration, 34.6% with 24-48 hours’ duration, and 25.5% with more than 48 hours.

A multivariable regression model identified absence of nonconvulsive SE with coma and a decreasing Charlson Comorbidity Index as the only independent predictors for return to baseline in patients with SE duration greater than 48 hours, and both remained significant predictors after adjustment for use of anesthetics and vasopressors. These predictors of a return to baseline after prolonged SE remained significant after excluding patients who died. This two-variable prediction model had an area under the receiver operating curve (AUROC) of 0.82, “indicating good discrimination,” and an AUROC of 0.76 following cross-validation.

The investigators also sought to develop a model to identify patients at risk for prolonged SE, but the model showed relatively poor discriminative ability with AUROCs of just 0.67-0.72 for predicting no termination of SE within 12, 24, or 48 hours. “Our attempt to generate a highly reliable prediction model for early recognition of patients at increased risk for developing prolonged SE failed, as demonstrated by the rather small AUROC and the fact that sensitivity analyses after exclusion of patients who died revealed inconsistent association of the identified predictors,” they wrote.

Prior reports identified younger age, absence of acute brain lesions at presentation, and the absence of multiple concomitant medical problems as factors associated with favorable outcome after prolonged SE, but “none of the studies performed multivariable regression models and generated or tested predictions models in this context,” they noted.

The authors cautioned that “although internal cross-validation of the final prediction model indicated adequate performance [based on an AUROC of 0.76], further external validation of our prediction model is warranted before our prediction model can be implemented and used for decision making in daily clinical practice.”

Some authors reported receiving research, travel, and/or personal grants or speaker fees from companies marketing antiepileptic drugs, such as UCB, Eisai, and GlaxoSmithKline.

[email protected]

SOURCE: Sutter RC et al. Epilepsia. 2018 Nov 22. doi: 10.1111/epi.14603

Two clinical parameters measurable at seizure onset appear to predict a return to baseline after prolonged status epilepticus (SE), based on a study of patients who presented to a single, tertiary academic medical center over a 12-year period.

Absence of nonconvulsive SE with coma and a decreasing Charlson Comorbidity Index were the only independent predictors for return to baseline in patients with SE duration greater than 48 hours, the researchers found. However, the research fell short of developing a model for identifying patients at risk for prolonged SE.

“These findings are of great clinical importance, as up to now, clinicians have had no reliable prediction tools to direct decisions regarding the level of care with progressive SE duration. Early and reliable identification of patients with potential favorable outcome despite having SE for several days is of utmost clinical importance, as this insight may urge clinicians to intensify treatment rather than consider care withdrawal as systemic and neurologic sequelae increase, and chances of SE termination decrease over time,” first author Raoul C. Sutter, MD, of University Hospital Basel (Switzerland), and his colleagues wrote about their findings in Epilepsia.

The researchers identified 467 adult patients with prolonged SE at University Hospital Basel during 2005-2016 – excluding those with SE as a consequence of hypoxic‐ischemic brain injury – who had a median age of 66.7 years and median SE duration of 1 day. While 11.8% of patients died in the hospital and 12.4% at 30 days after SE onset, 40.9% made a complete neurologic and functional recovery to their premorbid status.

There were significant differences in in-hospital outcomes between patients with different SE durations. For example, rates of returning to baseline differed significantly at 55.6% of those with a SE duration of 0-12 hours, 36.8% with 12-24 hours’ duration, 34.6% with 24-48 hours’ duration, and 25.5% with more than 48 hours.

A multivariable regression model identified absence of nonconvulsive SE with coma and a decreasing Charlson Comorbidity Index as the only independent predictors for return to baseline in patients with SE duration greater than 48 hours, and both remained significant predictors after adjustment for use of anesthetics and vasopressors. These predictors of a return to baseline after prolonged SE remained significant after excluding patients who died. This two-variable prediction model had an area under the receiver operating curve (AUROC) of 0.82, “indicating good discrimination,” and an AUROC of 0.76 following cross-validation.

The investigators also sought to develop a model to identify patients at risk for prolonged SE, but the model showed relatively poor discriminative ability with AUROCs of just 0.67-0.72 for predicting no termination of SE within 12, 24, or 48 hours. “Our attempt to generate a highly reliable prediction model for early recognition of patients at increased risk for developing prolonged SE failed, as demonstrated by the rather small AUROC and the fact that sensitivity analyses after exclusion of patients who died revealed inconsistent association of the identified predictors,” they wrote.

Prior reports identified younger age, absence of acute brain lesions at presentation, and the absence of multiple concomitant medical problems as factors associated with favorable outcome after prolonged SE, but “none of the studies performed multivariable regression models and generated or tested predictions models in this context,” they noted.

The authors cautioned that “although internal cross-validation of the final prediction model indicated adequate performance [based on an AUROC of 0.76], further external validation of our prediction model is warranted before our prediction model can be implemented and used for decision making in daily clinical practice.”

Some authors reported receiving research, travel, and/or personal grants or speaker fees from companies marketing antiepileptic drugs, such as UCB, Eisai, and GlaxoSmithKline.

[email protected]

SOURCE: Sutter RC et al. Epilepsia. 2018 Nov 22. doi: 10.1111/epi.14603

Trying to predict morbidity and mortality among patients with status epilepticus has proven difficult, and the 2 scoring metrics designed to accomplish that feat have significant shortcomings, according to a retrospective analysis of status epilepticus patients conducted at the Ohio State University Wexner Medical Center.

• Investigators reviewed the records of 46 affected patients admitted to the hospital’s neuro-critical care unit.
• Data from the status epilepticus Severity Score (STESS) and Epidemiology-based Mortality Score in Status Epilepticus (EMSE) were analyzed.
• Sensitivity of EMSE was 100% and sensitivity of STESS was 90%.
• The specificity of both metrics was wanting, however: EMSE, 28.6% and STESS, 42.9%.
• Researchers concluded that both scoring systems may help predict clinical outcomes in status epilepticus patients who have few co-existing conditions but are less valuable in populations with several medical problems.

Yechoor A, Adeli A, Hafeez S. External validation of the epidemiology-based mortality score in status epilepticus in an American intensive care population. Epilepsy Res. 2018;148:32-36.

Trying to predict morbidity and mortality among patients with status epilepticus has proven difficult, and the 2 scoring metrics designed to accomplish that feat have significant shortcomings, according to a retrospective analysis of status epilepticus patients conducted at the Ohio State University Wexner Medical Center.

• Investigators reviewed the records of 46 affected patients admitted to the hospital’s neuro-critical care unit.
• Data from the status epilepticus Severity Score (STESS) and Epidemiology-based Mortality Score in Status Epilepticus (EMSE) were analyzed.
• Sensitivity of EMSE was 100% and sensitivity of STESS was 90%.
• The specificity of both metrics was wanting, however: EMSE, 28.6% and STESS, 42.9%.
• Researchers concluded that both scoring systems may help predict clinical outcomes in status epilepticus patients who have few co-existing conditions but are less valuable in populations with several medical problems.

Yechoor A, Adeli A, Hafeez S. External validation of the epidemiology-based mortality score in status epilepticus in an American intensive care population. Epilepsy Res. 2018;148:32-36.

Trying to predict morbidity and mortality among patients with status epilepticus has proven difficult, and the 2 scoring metrics designed to accomplish that feat have significant shortcomings, according to a retrospective analysis of status epilepticus patients conducted at the Ohio State University Wexner Medical Center.

• Investigators reviewed the records of 46 affected patients admitted to the hospital’s neuro-critical care unit.
• Data from the status epilepticus Severity Score (STESS) and Epidemiology-based Mortality Score in Status Epilepticus (EMSE) were analyzed.
• Sensitivity of EMSE was 100% and sensitivity of STESS was 90%.
• The specificity of both metrics was wanting, however: EMSE, 28.6% and STESS, 42.9%.
• Researchers concluded that both scoring systems may help predict clinical outcomes in status epilepticus patients who have few co-existing conditions but are less valuable in populations with several medical problems.

Yechoor A, Adeli A, Hafeez S. External validation of the epidemiology-based mortality score in status epilepticus in an American intensive care population. Epilepsy Res. 2018;148:32-36.

Antiepileptic drugs were found to be linked with almost ninefold increased odds for two adverse skin reactions, Steven‐Johnson syndrome and toxic epidermal necrolysis, compared with non-AED medication classes in an analysis of adverse-event data from the Food and Drug Administration Adverse Event Reporting System.

Researchers at the University of Rhode Island College of Pharmacy in Kingston, who performed the retrospective study, also found that six drugs within the antiepileptic drug (AED) class had a reporting odds ratio estimate of more than 20, compared with other non-AEDs.

“Although several antiepileptic drugs have been associated with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), the class effect and impact of other AEDs are not well described,” Eric P. Borrelli, PharmD, and his colleagues reported in Epilepsia.

The investigators examined rates of SJS and TEN for several AEDs using adverse event data from the Food and Drug Administration Adverse Event Reporting System between July 2014 and December 2017. The study investigators examined 198 adverse reaction reports related to AEDs, which was greater than any other drug class.

Overall, AEDs as a group had a reporting odds ratio risk estimate of 8.7 (95% confidence interval, 7.5-10.2), compared with non-AEDs. Similarly, the proportional reporting ratio was found to be 8.7 (95% CI, 7.5-10.2) in the AED group.

Within the class, the medications with the highest risk were zonisamide, rufinamide, and clorazepate, which had about 70-, 60-, and 56-fold higher odds for SJS and TEN, compared with all other medications. Other high-risk AEDs in the group included lamotrigine (reporting odds ratio, 53.0), carbamazepine (reporting OR, 24.5), and phenytoin (reporting OR, 26.3).

“Greater than 90% of SJS [and] TEN reactions associated with AEDs occur within the first 2 months of treatment initiation, although some AEDs have been associated with such reactions during long‐term use,” the researchers wrote.

The authors acknowledged that measures of prevalence and incidence could not be determined from these data since the number of patients taking AEDs is unknown.

“Increased awareness of this risk among both prescribers and patients, particularly variations in risk among different AEDs, along with education on early recognition of SJS [and] TEN signs [and] symptoms, may help mitigate the number and severity of these adverse events,” the researchers concluded.

The study was partially funded by the Department of Veterans Affairs. One coauthor reported receiving research funding from Pfizer, Merck (Cubist), and The Medicines Company.

SOURCE: Borrelli EP et al. Epilepsia. 2018 Nov 5. doi: 10.1111/epi.14591.

Antiepileptic drugs were found to be linked with almost ninefold increased odds for two adverse skin reactions, Steven‐Johnson syndrome and toxic epidermal necrolysis, compared with non-AED medication classes in an analysis of adverse-event data from the Food and Drug Administration Adverse Event Reporting System.

Researchers at the University of Rhode Island College of Pharmacy in Kingston, who performed the retrospective study, also found that six drugs within the antiepileptic drug (AED) class had a reporting odds ratio estimate of more than 20, compared with other non-AEDs.

“Although several antiepileptic drugs have been associated with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), the class effect and impact of other AEDs are not well described,” Eric P. Borrelli, PharmD, and his colleagues reported in Epilepsia.

The investigators examined rates of SJS and TEN for several AEDs using adverse event data from the Food and Drug Administration Adverse Event Reporting System between July 2014 and December 2017. The study investigators examined 198 adverse reaction reports related to AEDs, which was greater than any other drug class.

Overall, AEDs as a group had a reporting odds ratio risk estimate of 8.7 (95% confidence interval, 7.5-10.2), compared with non-AEDs. Similarly, the proportional reporting ratio was found to be 8.7 (95% CI, 7.5-10.2) in the AED group.

Within the class, the medications with the highest risk were zonisamide, rufinamide, and clorazepate, which had about 70-, 60-, and 56-fold higher odds for SJS and TEN, compared with all other medications. Other high-risk AEDs in the group included lamotrigine (reporting odds ratio, 53.0), carbamazepine (reporting OR, 24.5), and phenytoin (reporting OR, 26.3).

“Greater than 90% of SJS [and] TEN reactions associated with AEDs occur within the first 2 months of treatment initiation, although some AEDs have been associated with such reactions during long‐term use,” the researchers wrote.

The authors acknowledged that measures of prevalence and incidence could not be determined from these data since the number of patients taking AEDs is unknown.

“Increased awareness of this risk among both prescribers and patients, particularly variations in risk among different AEDs, along with education on early recognition of SJS [and] TEN signs [and] symptoms, may help mitigate the number and severity of these adverse events,” the researchers concluded.

The study was partially funded by the Department of Veterans Affairs. One coauthor reported receiving research funding from Pfizer, Merck (Cubist), and The Medicines Company.

SOURCE: Borrelli EP et al. Epilepsia. 2018 Nov 5. doi: 10.1111/epi.14591.

Antiepileptic drugs were found to be linked with almost ninefold increased odds for two adverse skin reactions, Steven‐Johnson syndrome and toxic epidermal necrolysis, compared with non-AED medication classes in an analysis of adverse-event data from the Food and Drug Administration Adverse Event Reporting System.

Researchers at the University of Rhode Island College of Pharmacy in Kingston, who performed the retrospective study, also found that six drugs within the antiepileptic drug (AED) class had a reporting odds ratio estimate of more than 20, compared with other non-AEDs.

“Although several antiepileptic drugs have been associated with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), the class effect and impact of other AEDs are not well described,” Eric P. Borrelli, PharmD, and his colleagues reported in Epilepsia.

The investigators examined rates of SJS and TEN for several AEDs using adverse event data from the Food and Drug Administration Adverse Event Reporting System between July 2014 and December 2017. The study investigators examined 198 adverse reaction reports related to AEDs, which was greater than any other drug class.

Overall, AEDs as a group had a reporting odds ratio risk estimate of 8.7 (95% confidence interval, 7.5-10.2), compared with non-AEDs. Similarly, the proportional reporting ratio was found to be 8.7 (95% CI, 7.5-10.2) in the AED group.

Within the class, the medications with the highest risk were zonisamide, rufinamide, and clorazepate, which had about 70-, 60-, and 56-fold higher odds for SJS and TEN, compared with all other medications. Other high-risk AEDs in the group included lamotrigine (reporting odds ratio, 53.0), carbamazepine (reporting OR, 24.5), and phenytoin (reporting OR, 26.3).

“Greater than 90% of SJS [and] TEN reactions associated with AEDs occur within the first 2 months of treatment initiation, although some AEDs have been associated with such reactions during long‐term use,” the researchers wrote.

The authors acknowledged that measures of prevalence and incidence could not be determined from these data since the number of patients taking AEDs is unknown.

“Increased awareness of this risk among both prescribers and patients, particularly variations in risk among different AEDs, along with education on early recognition of SJS [and] TEN signs [and] symptoms, may help mitigate the number and severity of these adverse events,” the researchers concluded.

The study was partially funded by the Department of Veterans Affairs. One coauthor reported receiving research funding from Pfizer, Merck (Cubist), and The Medicines Company.

SOURCE: Borrelli EP et al. Epilepsia. 2018 Nov 5. doi: 10.1111/epi.14591.

SEATTLE – A novel extrasynaptic gamma-aminobutyric acid (GABA)–receptor agonist called OV-101 was safe and well-tolerated in adult and adolescent Angelman syndrome patients in a 12-week phase 2 trial. In a secondary analysis, the treatment appeared to improve sleep.

Jim Kling/MDedge News

Angelman syndrome is associated with a microdeletion on chromosome 15 encompassing the ubiquitin protein ligase E3a (UBE3A) gene. The resulting loss of expression of the UBE3A protein leads to increases in the uptake of GABA and reduces levels of extrasynaptic GABA. Patients with Angelman syndrome typically have motor dysfunction, often extreme: “These kids are very excitable, very active, and they have lots of trouble with sleep,” said Alex Kolevzon, MD, professor of psychiatry and pediatrics at the Icahn School of Medicine at Mount Sinai, in an interview.

Dr. Kolevzon presented the results at a poster session at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

The study was conducted at 12 sites in the United States and 1 in Israel. Ovid Pharmaceuticals plans to apply to the Food and Drug Administration later this year for approval. There is no existing drug for Angelman syndrome, and the study provided good safety reassurance. “There were some side effects, but for the most part we considered them mild, and only four (out of 88 subjects) discontinued because of side effects,” said Dr. Kolevzon.

The researchers used actigraphy to gain a more objective measure of sleep in the study participants. They randomized 88 patients with Angelman syndrome (aged 13-49 years) to receive placebo in the morning and 15 mg of OV-101 at night, 10 mg OVID-101 in the morning and 15 mg OVID-101 at night, or placebo both in the morning and at night.

Pyrexia occurred in 24% of the group who received the active drug only at night, 3% of the group given the twice-daily dose, and 7% of the placebo group. Seizures occurred in 7% of the once-daily group and 10% of the twice-daily group; seizures were not noted in the placebo group.

The main efficacy outcome measure was the Clinical Global Impressions-9 (CGI-9) scale. The once-daily group had a significant benefit in the sleep domain at 12 weeks, compared with placebo (difference, –0.77; P = .0141), but the twice-daily group had only a trend toward improvement in sleep (difference, –0.45; P = .1407).

Both active therapy groups had significant improvement in CGI-9 measures after 12 weeks of treatment compared to placebo – the twice-daily group (P = .0206, Fisher’s Exact Test) and the once-daily group (P = .0006, mixed model repeated measures analysis).

The actigraphy analysis, conducted in the 45% of patients who could tolerate its use, found that, compared to placebo, the once-daily dosing group experienced an 25.7 minute improvement in latency to sleep onset (P = .0147), as well an approximately 50 minute reduction in sleep time during the day, and a 3.65% improvement in sleep efficiency.

OV-101 has the potential to treat other conditions as well. “Obviously there are a lot of neurodevelopmental disorders where you see dysregulation between the GABAergic and glutamergic systems. This is a drug that has a unique effect on the GABAergic system. It’s already being studied in Fragile X syndrome, where we see this same kind of dysregulation and excess excitation,” said Dr. Kolevzon.

Dr. Kolevzon is a consultant for several drug companies including Ovid Therapeutics.
 

SOURCE: AACAP 2018. New Research Poster 3.1.

SEATTLE – A novel extrasynaptic gamma-aminobutyric acid (GABA)–receptor agonist called OV-101 was safe and well-tolerated in adult and adolescent Angelman syndrome patients in a 12-week phase 2 trial. In a secondary analysis, the treatment appeared to improve sleep.

Jim Kling/MDedge News

Angelman syndrome is associated with a microdeletion on chromosome 15 encompassing the ubiquitin protein ligase E3a (UBE3A) gene. The resulting loss of expression of the UBE3A protein leads to increases in the uptake of GABA and reduces levels of extrasynaptic GABA. Patients with Angelman syndrome typically have motor dysfunction, often extreme: “These kids are very excitable, very active, and they have lots of trouble with sleep,” said Alex Kolevzon, MD, professor of psychiatry and pediatrics at the Icahn School of Medicine at Mount Sinai, in an interview.

Dr. Kolevzon presented the results at a poster session at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

The study was conducted at 12 sites in the United States and 1 in Israel. Ovid Pharmaceuticals plans to apply to the Food and Drug Administration later this year for approval. There is no existing drug for Angelman syndrome, and the study provided good safety reassurance. “There were some side effects, but for the most part we considered them mild, and only four (out of 88 subjects) discontinued because of side effects,” said Dr. Kolevzon.

The researchers used actigraphy to gain a more objective measure of sleep in the study participants. They randomized 88 patients with Angelman syndrome (aged 13-49 years) to receive placebo in the morning and 15 mg of OV-101 at night, 10 mg OVID-101 in the morning and 15 mg OVID-101 at night, or placebo both in the morning and at night.

Pyrexia occurred in 24% of the group who received the active drug only at night, 3% of the group given the twice-daily dose, and 7% of the placebo group. Seizures occurred in 7% of the once-daily group and 10% of the twice-daily group; seizures were not noted in the placebo group.

The main efficacy outcome measure was the Clinical Global Impressions-9 (CGI-9) scale. The once-daily group had a significant benefit in the sleep domain at 12 weeks, compared with placebo (difference, –0.77; P = .0141), but the twice-daily group had only a trend toward improvement in sleep (difference, –0.45; P = .1407).

Both active therapy groups had significant improvement in CGI-9 measures after 12 weeks of treatment compared to placebo – the twice-daily group (P = .0206, Fisher’s Exact Test) and the once-daily group (P = .0006, mixed model repeated measures analysis).

The actigraphy analysis, conducted in the 45% of patients who could tolerate its use, found that, compared to placebo, the once-daily dosing group experienced an 25.7 minute improvement in latency to sleep onset (P = .0147), as well an approximately 50 minute reduction in sleep time during the day, and a 3.65% improvement in sleep efficiency.

OV-101 has the potential to treat other conditions as well. “Obviously there are a lot of neurodevelopmental disorders where you see dysregulation between the GABAergic and glutamergic systems. This is a drug that has a unique effect on the GABAergic system. It’s already being studied in Fragile X syndrome, where we see this same kind of dysregulation and excess excitation,” said Dr. Kolevzon.

Dr. Kolevzon is a consultant for several drug companies including Ovid Therapeutics.
 

SOURCE: AACAP 2018. New Research Poster 3.1.

SEATTLE – A novel extrasynaptic gamma-aminobutyric acid (GABA)–receptor agonist called OV-101 was safe and well-tolerated in adult and adolescent Angelman syndrome patients in a 12-week phase 2 trial. In a secondary analysis, the treatment appeared to improve sleep.

Jim Kling/MDedge News

Angelman syndrome is associated with a microdeletion on chromosome 15 encompassing the ubiquitin protein ligase E3a (UBE3A) gene. The resulting loss of expression of the UBE3A protein leads to increases in the uptake of GABA and reduces levels of extrasynaptic GABA. Patients with Angelman syndrome typically have motor dysfunction, often extreme: “These kids are very excitable, very active, and they have lots of trouble with sleep,” said Alex Kolevzon, MD, professor of psychiatry and pediatrics at the Icahn School of Medicine at Mount Sinai, in an interview.

Dr. Kolevzon presented the results at a poster session at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

The study was conducted at 12 sites in the United States and 1 in Israel. Ovid Pharmaceuticals plans to apply to the Food and Drug Administration later this year for approval. There is no existing drug for Angelman syndrome, and the study provided good safety reassurance. “There were some side effects, but for the most part we considered them mild, and only four (out of 88 subjects) discontinued because of side effects,” said Dr. Kolevzon.

The researchers used actigraphy to gain a more objective measure of sleep in the study participants. They randomized 88 patients with Angelman syndrome (aged 13-49 years) to receive placebo in the morning and 15 mg of OV-101 at night, 10 mg OVID-101 in the morning and 15 mg OVID-101 at night, or placebo both in the morning and at night.

Pyrexia occurred in 24% of the group who received the active drug only at night, 3% of the group given the twice-daily dose, and 7% of the placebo group. Seizures occurred in 7% of the once-daily group and 10% of the twice-daily group; seizures were not noted in the placebo group.

The main efficacy outcome measure was the Clinical Global Impressions-9 (CGI-9) scale. The once-daily group had a significant benefit in the sleep domain at 12 weeks, compared with placebo (difference, –0.77; P = .0141), but the twice-daily group had only a trend toward improvement in sleep (difference, –0.45; P = .1407).

Both active therapy groups had significant improvement in CGI-9 measures after 12 weeks of treatment compared to placebo – the twice-daily group (P = .0206, Fisher’s Exact Test) and the once-daily group (P = .0006, mixed model repeated measures analysis).

The actigraphy analysis, conducted in the 45% of patients who could tolerate its use, found that, compared to placebo, the once-daily dosing group experienced an 25.7 minute improvement in latency to sleep onset (P = .0147), as well an approximately 50 minute reduction in sleep time during the day, and a 3.65% improvement in sleep efficiency.

OV-101 has the potential to treat other conditions as well. “Obviously there are a lot of neurodevelopmental disorders where you see dysregulation between the GABAergic and glutamergic systems. This is a drug that has a unique effect on the GABAergic system. It’s already being studied in Fragile X syndrome, where we see this same kind of dysregulation and excess excitation,” said Dr. Kolevzon.

Dr. Kolevzon is a consultant for several drug companies including Ovid Therapeutics.
 

SOURCE: AACAP 2018. New Research Poster 3.1.

Among people with Alzheimer Disease, the risk of developing a stroke is significantly greater if they are using antiepileptic drugs, according to a large study published in the Journal of the American Heart Association.

• The Medication Use and Alzheimer’s Disease cohort, which includes all the people in Finland who have been clinically diagnosed with Alzheimer disease (70,718) from 2005 to 2011, was analyzed to look for a correlation between the disease and antiepileptic drug use.
• Patients who had used the medications were about 37% more likely to have experienced a stroke, compared to nondrug users (hazard ratio [HR], 1.37).
• The likelihood of having a stroke in this patient population was greatest during the first 3 months of taking antiepileptic medication (HR, 2.36).
• The association between drug use and ischemic stroke was less than that observed between drug use and hemorrhagic stroke (HR, 1.34 vs 1.44).

Sarycheva T, Lavikainen P, Taipale H, et al. Antiepileptic Drug Use and the Risk of Stroke Among Community-Dwelling People with Alzheimer Disease: A Matched Cohort Study. J Am Heart Assoc. 2018; 7: e009742. DOI: 10.1161/JAHA.118.009742.

Among people with Alzheimer Disease, the risk of developing a stroke is significantly greater if they are using antiepileptic drugs, according to a large study published in the Journal of the American Heart Association.

• The Medication Use and Alzheimer’s Disease cohort, which includes all the people in Finland who have been clinically diagnosed with Alzheimer disease (70,718) from 2005 to 2011, was analyzed to look for a correlation between the disease and antiepileptic drug use.
• Patients who had used the medications were about 37% more likely to have experienced a stroke, compared to nondrug users (hazard ratio [HR], 1.37).
• The likelihood of having a stroke in this patient population was greatest during the first 3 months of taking antiepileptic medication (HR, 2.36).
• The association between drug use and ischemic stroke was less than that observed between drug use and hemorrhagic stroke (HR, 1.34 vs 1.44).

Sarycheva T, Lavikainen P, Taipale H, et al. Antiepileptic Drug Use and the Risk of Stroke Among Community-Dwelling People with Alzheimer Disease: A Matched Cohort Study. J Am Heart Assoc. 2018; 7: e009742. DOI: 10.1161/JAHA.118.009742.

Among people with Alzheimer Disease, the risk of developing a stroke is significantly greater if they are using antiepileptic drugs, according to a large study published in the Journal of the American Heart Association.

• The Medication Use and Alzheimer’s Disease cohort, which includes all the people in Finland who have been clinically diagnosed with Alzheimer disease (70,718) from 2005 to 2011, was analyzed to look for a correlation between the disease and antiepileptic drug use.
• Patients who had used the medications were about 37% more likely to have experienced a stroke, compared to nondrug users (hazard ratio [HR], 1.37).
• The likelihood of having a stroke in this patient population was greatest during the first 3 months of taking antiepileptic medication (HR, 2.36).
• The association between drug use and ischemic stroke was less than that observed between drug use and hemorrhagic stroke (HR, 1.34 vs 1.44).

Sarycheva T, Lavikainen P, Taipale H, et al. Antiepileptic Drug Use and the Risk of Stroke Among Community-Dwelling People with Alzheimer Disease: A Matched Cohort Study. J Am Heart Assoc. 2018; 7: e009742. DOI: 10.1161/JAHA.118.009742.

Standard depth invasive electrodes are typically used to precisely locate areas of the brain that are responsible for seizures in patients with medically refractory epilepsy, but a recent analysis suggests that hybrid depth microwire electrodes may be just as effective and just as safe.

• Investigators at Cedars-Sinai Medical Center reviewed 53 cases of refractory epilepsy who had surgery between 2006 and 2017.
• The analysis included 555 electrodes and revealed a complication rate of 2.3% per electrode and a per case rate of 20.8%; no infections or deaths were reported.
• The researchers did not uncover a difference in complication rates between standard and hybrid depth electrodes.
• Hybrid depth electrodes were as reliable as standard electrodes in pinpointing seizure onset zones.

Carlson AA, Rutishauser U, Mamelak AN. Safety and utility of hybrid depth electrodes for seizure localization and single-unit neuronal recording [published online ahead of print Oct 16, 2018]. Stereotact Funct Neurosurg.

Standard depth invasive electrodes are typically used to precisely locate areas of the brain that are responsible for seizures in patients with medically refractory epilepsy, but a recent analysis suggests that hybrid depth microwire electrodes may be just as effective and just as safe.

• Investigators at Cedars-Sinai Medical Center reviewed 53 cases of refractory epilepsy who had surgery between 2006 and 2017.
• The analysis included 555 electrodes and revealed a complication rate of 2.3% per electrode and a per case rate of 20.8%; no infections or deaths were reported.
• The researchers did not uncover a difference in complication rates between standard and hybrid depth electrodes.
• Hybrid depth electrodes were as reliable as standard electrodes in pinpointing seizure onset zones.

Carlson AA, Rutishauser U, Mamelak AN. Safety and utility of hybrid depth electrodes for seizure localization and single-unit neuronal recording [published online ahead of print Oct 16, 2018]. Stereotact Funct Neurosurg.

Standard depth invasive electrodes are typically used to precisely locate areas of the brain that are responsible for seizures in patients with medically refractory epilepsy, but a recent analysis suggests that hybrid depth microwire electrodes may be just as effective and just as safe.

• Investigators at Cedars-Sinai Medical Center reviewed 53 cases of refractory epilepsy who had surgery between 2006 and 2017.
• The analysis included 555 electrodes and revealed a complication rate of 2.3% per electrode and a per case rate of 20.8%; no infections or deaths were reported.
• The researchers did not uncover a difference in complication rates between standard and hybrid depth electrodes.
• Hybrid depth electrodes were as reliable as standard electrodes in pinpointing seizure onset zones.

Carlson AA, Rutishauser U, Mamelak AN. Safety and utility of hybrid depth electrodes for seizure localization and single-unit neuronal recording [published online ahead of print Oct 16, 2018]. Stereotact Funct Neurosurg.